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Comprehensive Molecular Characterization of a Large Series of Calcified Chondroid Mesenchymal Neoplasms Widening Their Morphologic Spectrum. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-08-15 Clément Benard, François Le Loarer, Anne Gomez-Mascard, Rihab Azmani, Jeremy Garcia, Raul Perret, Gonzague de Pinieux, Elodie Miquelestorena-Standley, Noelle Weingertner, Marie Karanian, Alexandra Meurgey, Audrey Michot, Franck Tirode, Nathalene Truffaux, Nicolas Macagno, Corinne Bouvier
Recently, FN1 fusions to receptor tyrosine kinase genes have been identified in soft tissue tumors with calcified chondroid matrix named calcifying chondroid mesenchymal neoplasms (CCMNs). We collected 33 cases of CCMN from the French network for soft tissue and bone tumors. We performed whole-exome RNA sequencing, expression analysis, and genome-wide DNA methylation profiling in 33, 30, and 20 cases
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Sinonasal Squamous Cell Carcinoma with DEK::AFF2 Rearrangement: An Aggressive Cancer with Bland Morphology. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-08-12 Aude Trinquet, Marick Laé, Charles Lépine, Marie-Delphine Lanic, Vanessa Lacheretz-Szablewski, Caroline Shaar Chneker, Jean-Michel Goujon, Valentin Favier, Valérie Costes-Martineau
DEK::AFF2 squamous cell carcinoma is a recently described cancer entity, with 29 cases reported to date. Occasionally, these carcinomas appear deceptively indistinguishable; however, specific morphological and phenotypic features suggest the presence of this rearrangement. However, the prognostic value of this diagnosis remains unclear. We aimed to report a new case series with histological, molecular
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Prevalence of S-methyl-5'-thioadenosine Phosphorylase (MTAP) Deficiency in Human Cancer: A Tissue Microarray Study on 13,067 Tumors From 149 Different Tumor Types. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-08-12 Natalia Gorbokon, Niklas Wößner, Maximilian Lennartz, Sebastian Dwertmann Rico, Simon Kind, Viktor Reiswich, Florian Viehweger, Florian Lutz, Christoph Fraune, Andreas M Luebke, Claudia Hube-Magg, Anne Menz, Ria Schlichter, Till Krech, Andrea Hinsch, Eike Burandt, Guido Sauter, Ronald Simon, Stefan Steurer, Andreas H Marx, Patrick Lebok, David Dum, Sarah Minner, Frank Jacobsen, Till S Clauditz, Thilo
Loss of S-methyl-5'-thioadenosine phosphorylase (MTAP) expression is a common event in cancer leading to a critical vulnerability of cancer cells towards anti-cancer drugs. Homozygous MTAP deletions result in a complete expression loss that can be detected by immunohistochemistry (IHC). In this study, a tissue microarray containing 17,078 samples from 149 different tumor entities was analyzed by IHC
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Spinal Cord Astroblastoma With EWSR1-BEND2 Fusion in Female Patients: A Report of Four Cases From China and a Comprehensive Literature Review. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-08-06 Lingyi Fu, I Weng Lao, Liyun Huang, Liqiong Ou, Lei Yuan, Ziteng Li, Shuo Li, Wanming Hu, Shaoyan Xi
Astroblastoma is an extremely rare central nervous system tumor characterized by astroblastic pseudorosettes and vascular hyalinization. Despite these histologic hallmarks, its morphology can vary, occasionally resembling other central nervous system tumors such as ependymoma. A novel tumor entity, astroblastoma, meningioma 1 (MN1)-altered, has been identified, featuring MN1 gene rearrangements typically
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p53 Immunohistochemistry Defines a Subset of Human Papillomavirus-Independent Penile Squamous Cell Carcinomas With Adverse Prognosis. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-07-23 Isabel Trias, Ferran Algaba, Inés de Torres, Adela Saco, Lorena Marimon, Núria Peñuelas, Laia Diez-Ahijado, Lia Sisuashvili, Katarzyna Darecka, Alba Morató, Marta Del Pino, Carla Ferrándiz-Pulido, María José Ribal, Tarek Ajami, Juan Manuel Corral, Josep Maria Gaya, Oscar Reig, Oriol Ordi, Inmaculada Ribera-Cortada, Adriana García-Herrera, Natalia Rakislova
Penile squamous cell carcinoma (PSCC) is classified into 2 prognostically distinct types: human papillomavirus (HPV)-associated and HPV-independent. However, the impact of p53 status on prognosis remains controversial. We correlated HPV and p53 status with the prognosis of a large series of patients with PSCC. p53 was analyzed according to a recently described immunohistochemical (IHC) pattern-based
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Pancreatic and Ileal Neuroendocrine Tumors: Metastatic Disease or a Novel MEN Syndrome? Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-07-22 Sylvia L Asa, Amr Mohamed
Multiple endocrine neoplasms are a feature of multiple endocrine neoplasia (MEN) syndromes types 1, 2, 4, and 5. However, the ileum is not usually involved in these disorders. We report a series of patients with neuroendocrine tumors (NETs) involving both the pancreas and the ileum. We searched the laboratory information system and personal consultation records of the authors from 2019 to 2023 for
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Risk Factors of Lymph Node Metastasis and Prognosis in 891 Chinese Patients With Submucosal Early Gastric Carcinoma, Emphasizing Differences Between Gastric Cardiac and Noncardiac Origins. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-07-19 Yuqing Cheng, Mingzhan Du, Yaohui Wang, Ting Li, Chongfang He, Xiaoli Zhou, Min Lin, Qin Huang
Differences in risk factors (RF) of lymph node metastasis (LNM) and prognosis between submucosal early gastric cardiac (SEGCC) and noncardiac (SEGNCC) carcinomas remain unclear. In this study, we investigated and compared RF of LNM and prognosis in 891 patients with radical gastrectomy for SEGCC (n=217) or SEGNCC (n=674). Compared with SEGNCC, SEGCC displayed significantly higher proportion of elderly
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High-grade Anaplastic Transformation of Ovarian Serous Borderline Tumor: A Distinctive Morphology With Abundant Dense Eosinophilic Cytoplasm and Dismal Prognosis. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-07-19 Xiaoming Zhang, Kelly A Devereaux, Emily Ryan, Fei Fei, Christian A Kunder, Teri A Longacre
Ovarian serous borderline tumors (SBTs) have a generally favorable prognosis. Although the risk of progression to low-grade serous carcinoma is well documented, progression to high-grade carcinoma is rare. We report the clinicopathologic features of seven SBTs, each associated with the presence of a morphologically unique high-grade component with an extremely dismal prognosis. All of the SBTs exhibited
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Reporting of Incidental Thrombotic Arteriopathy in Lung Resection Specimens: Examination of Clinical Impact. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-07-17 Andréanne Gagné, Robert F Padera, Rachel K Putman, Lynette M Sholl
Pulmonary thrombotic arteriopathy (PTA) can be an incidental finding in lung resections performed for various indications. Historic studies largely examined PTA in autopsies. Thus, the prevalence in surgical samples, particularly in the modern era of lung cancer screening, is poorly defined. Detection of PTA in surgical samples may provide an opportunity for therapeutic intervention, but the impact
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Assessment of Interobserver Agreement Among Gynecologic Pathologists Between Three-Tier Versus Binary Pattern-based Classification Systems for HPV-associated Endocervical Adenocarcinoma. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-07-17 Roman E Zyla, David W Dodington, Sara Pakbaz, Tatjana Terzic, Carrie Robinson, Blaise Clarke, Marjan Rouzbahman, Anjelica Hodgson
The three-tier (A vs. B vs. C) pattern-based (Silva) classification system is a strong and fairly reproducible predictor of the risk of lymph node involvement and recurrence of human papillomavirus (HPV)-associated endocervical adenocarcinoma (EA). Recently, a binary pattern-based classification system has been proposed which incorporates the Silva pattern and lymphovascular invasion (LVI) to assign
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PD-L1 Expression and Its Modulating Factors in Anaplastic Thyroid Carcinoma: A Multi-institutional Study. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-07-15 Shipra Agarwal, Chan Kwon Jung, Pranitha Gaddam, Mitsuyoshi Hirokawa, Takuya Higashiyama, Jen-Fan Hang, Wei-An Lai, Somboon Keelawat, Zhiyan Liu, Hee Young Na, So Yeon Park, Junya Fukuoka, Shinya Satoh, Zhanna Mussazhanova, Masahiro Nakashima, Kennichi Kakudo, Andrey Bychkov
Anti-PD immunotherapy is currently under investigation in anaplastic thyroid carcinoma (ATC). Tumor cell surface PD-L1 expression is considered predictive of therapeutic response. Although papillary thyroid carcinoma has been widely studied for PD-L1 expression, there are limited data on ATC. In this retrospective multi-institutional study involving 9 centers across Asia, 179 ATCs were assessed for
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Establishing Criteria for Tumor Necrosis as Prognostic Indicator in Colorectal Cancer. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-07-15 Meeri Kastinen, Päivi Sirniö, Hanna Elomaa, Ville K Äijälä, Henna Karjalainen, Vilja V Tapiainen, Vesa-Matti Pohjanen, Janette Kemppainen, Katja Sliashynskaya, Maarit Ahtiainen, Jukka Rintala, Sanna Meriläinen, Tero Rautio, Juha Saarnio, Taneli T Mattila, Outi Lindgren, Erkki-Ville Wirta, Olli Helminen, Toni T Seppälä, Jan Böhm, Jukka-Pekka Mecklin, Anne Tuomisto, Markus J Mäkinen, Juha P Väyrynen
Tumor necrosis has been reported to represent an independent prognostic factor in colorectal cancer, but its evaluation methods have not been described in sufficient detail to introduce tumor necrosis evaluation into clinical use. To study the potential of tumor necrosis as a prognostic indicator in colorectal cancer, criteria for 3 methods for its evaluation were defined: the average percentage method
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PRAME Expression in Merkel Cell Carcinoma. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-07-12 Elisabeth Miller, Andrew Biesemier, David M Coomes, Shyam S Raghavan
Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor of the skin. Risk factors include extensive sun damage, infection with Merkel cell polyomavirus, and an immunocompromised state. PRAME, also known as preferentially expressed antigen in melanoma, is a cancer-testis antigen recently found to be a useful diagnostic tool in the workup of melanocytic neoplasms. However, the expression
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Inflammatory Giant Cell Carcinoma of the Lung: Clinicopathologic, Immunohistochemical, and Next-generation Sequencing Study of 14 Cases. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-07-11 David I Suster, A Craig Mackinnon, Natali Ronen, Haider A Mejbel, Shuko Harada, Michael Michal, Saul Suster
A distinctive histological variant of poorly differentiated, sarcomatoid, non-small cell lung carcinoma characterized by a discohesive population of giant tumor cells associated with prominent interstitial inflammatory cell infiltrates is described. The tumors occurred in 7 women and 7 men, 42 to 72 years of age (mean: 56 y). They predominantly affected the upper lobes and measured 1.3 to 9 cm in greatest
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Clear Cell Carcinomas of Müllerian Type and Rete Testis Origin Presenting as Scrotal Masses: A Study of Seven Cases. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-07-11 Irem Kilic, Andrés M Acosta, Thomas M Ulbright
Ovarian-type epithelial tumors involving the testis and paratestis are rare, with clear cell carcinomas (CCC) one of the least frequent. We report our experience with 4 müllerian-type (MT) CCCs presenting as testicular/scrotal masses and arising in the paratestis (n=2) and seminal vesicle (n=2; well supported in 1 case and likely in the other). In addition, we document 3 cases of papillary CCC exclusively
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ALK-rearranged Mesenchymal Neoplasms With Prominent Foamy/Pseudolipogenic Cell Morphology: Expanding the Phenotypic Spectrum of ALK Fusion Neoplasms and Report of Novel Fusion Partners. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-07-09 Abbas Agaimy, Robert Stoehr, Cyril Fisher, John S A Chrisinger, Elizabeth G Demicco, Lars Tögel, Michal Michal, Michael Michal
The category of ALK-rearranged mesenchymal neoplasms has been evolving rapidly, with reports of morphologically diverse lesions of cutaneous, soft tissue, and visceral origin. While some of these represent morphologically defined entities harboring recurrent ALK fusions (inflammatory myofibroblastic tumor and epithelioid fibrous histiocytoma), others are unclassified by morphology with variable overlap
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Cytoplasmic Lipid Droplets Predict Worse Prognosis in Diffuse Large B-Cell Lymphoma: Next-Generation Sequencing Deciphering Lipogenic Genes. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-07-09 Shu-Hsien Wang, Po-Min Chiang, Yung-Yeh Su, Yu-Ting Yu, Ya-Ping Chen, Tsai-Yun Chen, L Jeffrey Medeiros, Chang-Yao Chu, Peng-Chieh Chen, Kung-Chao Chang
Burkitt lymphoma is characterized by high cell turnover and numerous cytoplasmic vacuoles that are demonstrated to be lipid droplets (LDs) decorated by adipophilin. By contrast, cytoplasmic vacuoles are variably observed in diffuse large B-cell lymphoma (DLBCL) and less well characterized. In this study, we first validated in DLBCL that cytoplasmic vacuoles are indeed LDs by Oil-red-O stain, Bodipy
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Reproducibility of c-Met Immunohistochemical Scoring (Clone SP44) for Non-Small Cell Lung Cancer Using Conventional Light Microscopy and Whole Slide Imaging. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-07-08 Christophe Bontoux, Véronique Hofman, Emmanuel Chamorey, Renaud Schiappa, Sandra Lassalle, Elodie Long-Mira, Katia Zahaf, Salomé Lalvée, Julien Fayada, Christelle Bonnetaud, Samantha Goffinet, Marius Ilié, Paul Hofman
Emerging therapies for non-small cell lung cancer targeting c-Met overexpression have recently demonstrated promising results. However, the evaluation of c-Met expression can be challenging. We aimed to study the inter and intraobserver reproducibility of c-Met expression evaluation. One hundred ten cases with non-small cell lung cancer (40 biopsies and 70 surgical specimens) were retrospectively selected
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Embryoid Bodies and Related Proliferations in Ovarian Germ Cell Tumors. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-07-04 Kyle M Devins, Robert H Young
We investigated the frequency and associated pathology of embryoid bodies in ovarian tumors by evaluating neoplasms in which they are known to occur: 100 immature teratomas, 125 malignant mixed germ cell tumors, and 6 polyembryomas. Three immature teratomas contained a single relatively well-formed embryoid body, whereas these and 11 others showed foci we categorized as embryoid body remnants consisting
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Artificial Intelligence-based Segmentation of Residual Pancreatic Cancer in Resection Specimens Following Neoadjuvant Treatment (ISGPP-2): International Improvement and Validation Study. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-07-02 Boris V Janssen, Bart Oteman, Mahsoem Ali, Pieter A Valkema, Volkan Adsay, Olca Basturk, Deyali Chatterjee, Angela Chou, Stijn Crobach, Michael Doukas, Paul Drillenburg, Irene Esposito, Anthony J Gill, Seung-Mo Hong, Casper Jansen, Mike Kliffen, Anubhav Mittal, Jas Samra, Marie-Louise F van Velthuysen, Aslihan Yavas, Geert Kazemier, Joanne Verheij, Ewout Steyerberg, Marc G Besselink, Huamin Wang, Caroline
Neoadjuvant therapy (NAT) has become routine in patients with borderline resectable pancreatic cancer. Pathologists examine pancreatic cancer resection specimens to evaluate the effect of NAT. However, an automated scoring system to objectively quantify residual pancreatic cancer (RPC) is currently lacking. Herein, we developed and validated the first automated segmentation model using artificial intelligence
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Intraductal Implantation of Biliary Neoplasms: A Potential Cause of "Multifocal" Tumors. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-07-01 Yoh Zen, Masayuki Akita, Evangelia Florou, Takumi Fukumoto, Tomoo Itoh, Evangelos Prassas, Krishna Menon, Parthi Srinivasan
Multiple biliary tumors rarely develop in patients without underlying chronic hepatobiliary disease. Those lesions are regarded as multifocal neoplasms if there is no interconnecting dysplasia. This study aimed to determine whether 2 separate tumors in the biliary tract represent true multifocal independent tumorigenesis or intraluminal implantation of a single neoplasm. Two separate biliary tumors
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Expanding the Spectrum of NUTM1-Rearranged Sarcoma: A Clinicopathologic and Molecular Genetic Study of 8 Cases. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-07-01 Peipei Zhu, Ke Sun, I Weng Lao, Lin Yu, Qianming Bai, Xiaoyan Zhou, Jian Wang
Apart from the lethal midline carcinoma (NUT carcinoma), NUTM1 translocation has also been reported in mesenchymal tumors, but is exceedingly rare. Here, we describe a series of 8 NUTM1-rearranged sarcomas to further characterize the clinicopathologic features of this emerging entity. This cohort included 2 males and 6 females with age ranging from 24 to 64 years (mean: 51 y; median: 56 y). Tumors
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Tubulocystic Carcinoma of Bile Ducts: A Distinct Type of Cholangiocarcinoma Associated With Adenofibroma-type Lesions. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-07-01 Francesca Masetto, Andrea Mafficini, Burcu Saka, Ayse Armutlu, Deyali Chatterjee, Kee-Taek Jang, Yoh Zen, Pooja Navale, Matteo Fassan, Carlos E Bacchi, Paola Mattiolo, Michele Simbolo, Andrea Ruzzenente, Rita T Lawlor, Michelle Reid, Olca Basturk, Volkan Adsay, Aldo Scarpa, Claudio Luchini
A type of cholangiocarcinoma (CCA) characterized by peculiar histologic patterns and underlying adenofibromatous lesions has been reported in the literature mostly as individual case reports. This study aims to further clarify the defining characteristics of this spectrum of lesions. Clinicopathologic analysis of 8 biliary tumors with tubulocystic architecture arising in the background of adenofibroma-type
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Characteristics and Clinical Value of MYC, BCL2, and BCL6 Rearrangement Detected by Next-generation Sequencing in DLBCL. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-06-28 Yupeng Zeng, Ran Wei, Longlong Bao, Tian Xue, Yulan Qin, Min Ren, Qianming Bai, Qianlan Yao, Chengli Yu, Chen Chen, Ping Wei, Baohua Yu, Junning Cao, Xiaoqiu Li, Qunling Zhang, Xiaoyan Zhou
MYC, BCL2, and BCL6 rearrangements are clinically important events of diffuse large B-cell lymphoma (DLBCL). The ability and clinical value of targeted next-generation sequencing (NGS) in the detection of these rearrangements in DLBCL have not been fully determined. We performed targeted NGS (481-gene-panel) and break-apart FISH of MYC, BCL2, and BCL6 gene regions in 233 DLBCL cases. We identified
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Intra-ampullary Papillary Tubular Neoplasm (IAPN): Clinicopathologic Analysis of 72 Cases Highlights the Distinctive Characteristics of a Poorly Recognized Entity. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-06-28 Zeynep C Tarcan, Rohat Esmer, Kadriye E Akar, Pelin Bagci, Emine Bozkurtlar, Burcu Saka, Ayse Armutlu, Hulya Sahin Ozkan, Kerem Ozcan, Orhun C Taskin, Yersu Kapran, Cisel Aydin Mericoz, Serdar Balci, Serpil Yilmaz, Duygu Cengiz, Bengi Gurses, Emrah Alper, Gurkan Tellioglu, Emre Bozkurt, Orhan Bilge, Jeanette D Cheng, Olca Basturk, N Volkan Adsay
The guidelines recently recognized the intra-ampullary papillary tubular neoplasm (IAPN) as a distinct tumor entity. However, the data on IAPN and its distinction from other ampullary tumors remain limited. A detailed clinicopathologic analysis of 72 previously unpublished IAPNs was performed. The patients were: male/female=1.8; mean age=67 years (range: 42 to 86 y); mean size=2.3 cm. Gross-microscopic
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Validation Study of the Newly Proposed Refined Diagnostic Criteria for Malignant Phyllodes Tumor With 136 Borderline and Malignant Phyllodes Tumor Cases. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-06-27 Xiaoxian Li, Thi Truc Anh Nguyen, Jilun Zhang, Anupma Nayak, Yi Liu, Lauren A Duckworth, Gloria Zhang, Rania Bakkar, Indu Agarwal, Yanjun Hou, Hua Guo, Xiao Huang, Shi Wei, Sayeeda Yasmeen, Khoury Thaer, Huifeng Huang, Huina Zhang, Geoffrey Hughes Smith, Gulisa Turashvili, Limin Peng, Yueping Liu, Wentao Yang, Kalliopi P Siziopikou
The World Health Organization (WHO) diagnostic criteria for malignant phyllodes tumor (MPT) may miss a significant number of MPTs with metastatic potential. New refined diagnostic criteria (Refined Criteria) for MPT were recently proposed. The aim of this study is to validate the Refined Criteria. This validation study included 136 borderline (borderline phyllodes tumor [BoPT]) and MPT cases that were
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PEComa With MITF Overexpression: Clinicopathologic and Molecular Analysis of a Series of 36 Cases. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-06-27 John Hanna, Eleanor Russell-Goldman, Esther Baranov, Daniel Pissaloux, Yvonne Y Li, Franck Tirode, Arnaud de la Fouchardiere, Christopher D M Fletcher
Perivascular epithelioid cell neoplasms (PEComas) are tumors of uncertain cell lineage that occur across a wide age range, at a variety of anatomic sites, and with a female predominance. Most PEComas are associated with dysregulation of the mTOR pathway, most commonly through inactivating mutations of TSC2 or TSC1. However, a small subset of PEComas are instead associated with TFE3 gene fusions. MITF
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A Comprehensive Clinicopathologic and Molecular Reappraisal of GLI1-altered Mesenchymal Tumors with Pooled Outcome Analysis Showing Poor Survival in GLI1- amplified Versus GLI1-rearranged Tumors. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-06-27 Carla Saoud, Abbas Agaimy, Josephine K Dermawan, Jie-Fu Chen, Marc K Rosenblum, Brendan C Dickson, Nooshin Dashti, Michael Michal, Kemal Kosemehmetoglu, Nasir Ud Din, Karen Albritton, Narasimhan P Agaram, Cristina R Antonescu
GLI1-altered mesenchymal tumor is a recently described distinct pathologic entity with an established risk of malignancy, being defined molecularly by either GLI1 gene fusions or amplifications. The clinicopathologic overlap of tumors driven by the 2 seemingly distinct mechanisms of GLI1 activation is still emerging. Herein, we report the largest series of molecularly confirmed GLI1-altered mesenchymal
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Female Adnexal Tumor of Probable Wolffian Origin (Wolffian Tumor): A Potential Mimic of Peritoneal Mesothelioma. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-06-26 Kianoosh Keyhanian, Tanner Mack, Erna Forgo, Henry Tazelaar, Teri A Longacre
Wolffian tumor and its nosologic relative, the recently defined STK11 adnexal tumor are rare neoplasms thought to arise from mesonephric remnants. These tumors typically arise in the broad ligament, fallopian tube, and ovarian hilum and although most are associated with a good prognosis, up to 50% of STK11 adnexal tumors demonstrate aggressive clinical behavior. The chief differential diagnoses include
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Comparative Whole-Genome Sequencing Analysis of In-situ and Invasive Acral Lentiginous Melanoma: Markedly Increased Copy Number Gains of GAB2, PAK1, UCP2, and CCND1 are Associated with Melanoma Invasion. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-06-25 Hyung Keon Park, Yoo Duk Choi, Hyun Jeong Shim, Yoonjoo Choi, Ik Joo Chung, Sook Jung Yun
Acral lentiginous melanoma (ALM) is the most common subtype of acral melanoma. Even though recent genetic studies are reported in acral melanomas, the genetic differences between in-situ and invasive ALM remain unclear. We aimed to analyze specific genetic changes in ALM and compare genetic differences between in-situ and invasive lesions to identify genetic changes associated with the pathogenesis
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DICER1 Mutations Define the Landscape of Poorly Differentiated Thyroid Carcinoma in Children and Young Adults: Case Report and Literature Review. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-06-24 Jonas Ver Berne, Annick Van den Bruel, Stefanie Vermeire, Pascale De Paepe
Poorly differentiated thyroid carcinoma (PDTC) is a rare malignancy, representing ~1% of all thyroid tumors. It is characterized by high-grade histologic features without the anaplastic characteristics observed in anaplastic thyroid carcinoma. Although rare in children and young adults, there is emerging evidence of clinical and genetic differences with PDTC in adults. We present a case of a 19-year-old
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Dysplasia Detected in Patients With Serrated Epithelial Change Is Frequently Associated With an Invisible or Flat Endoscopic Appearance, Nonconventional Dysplastic Features, and Advanced Neoplasia. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-06-21 Dorukhan Bahceci, Lindsay Alpert, Tanner Storozuk, Xiaoyan Liao, Masato Yozu, Maria Westerhoff, Bence P Kővári, Gregory Y Lauwers, Won-Tak Choi
The significance of serrated epithelial change (SEC), defined as endoscopically invisible hyperplastic polyp (HP)-like mucosal change identified in patients with inflammatory bowel disease (IBD), remains unclear. Although some studies reported an increased risk of synchronous and/or metachronous colorectal neoplasia in patients with SEC, including advanced neoplasia (high-grade dysplasia or colorectal
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Clinical and Histopathologic Characteristics of Acute Severe Hepatitis Associated With Human Herpesvirus 6 Infection. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-06-21 Huiying Wang, Annette Vannilam, Einar T Hafberg, Lynette A Gillis, Ari Kassardjian, Bita V Naini, Vinay Prasad, David R Kelly, Elizabeth C Mroczek-Musulman, Konstance Knox, Hernan Correa, Jiancong Liang
Acute severe hepatitis associated with active human herpesvirus 6 (HHV-6) infection is a rare life-threatening condition with unclear clinical course and histopathology. In this study, we retrospectively analyzed 5 patients with indeterminate acute severe hepatitis found to have active hepatic HHV-6 infection during care. All patients were previously healthy children presenting with a nonspecific prodrome
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Stage III Melanoma: A Proposed Staging Model That Outperforms the American Joint Committee on Cancer Eighth Edition Staging System. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-06-20 Alexandra Balaban, Kasey J McCollum, Rami N Al-Rohil
National Comprehensive Cancer Network guidelines state that clinical stage III melanoma patients may undergo ultrasound surveillance of the nodal basin in lieu of complete lymph node dissection (CLND). This has led to an inability to accurately classify patients according to the American Joint Committee on Cancer (AJCC) eighth edition staging system because it uses the total number of positive lymph
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Histopathologic and Clinical Characterization of Brentuximab Vedotin-associated Rash. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-06-20 Saisindhu Narala, Atif Saleem, Ryanne A Brown, Roberto A Novoa, Youn H Kim, Kerri E Rieger
Rash is one of the commonly observed adverse events with brentuximab vedotin (BV), a CD30-targeted antibody-drug conjugate used to treat cutaneous T-cell lymphoma (CTCL). However, clinical and histopathologic characterization of BV-associated rash (BVAR) is limited. Distinguishing BVAR from a patient's underlying CTCL can be challenging and can lead to treatment interruptions or even premature drug
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PRKC Fusion Melanocytic Tumors, a Subgroup of Melanocytic Tumors More Closely Aligned to Blue Nevi Than to PRKAR1A-inactivated Pigmented Epithelioid Melanocytomas. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-06-12 Pragi Patel, Alice Chen, Natasha Sharma, Yongzhan Zhang, Victor L Quan, Shantel Olivares, Pedram Gerami
Tumors morphologically classified as pigmented epithelioid melanocytomas (PEMs) are genomically diverse, with the 2 most common genomic subtypes being PRKC fusions or PRKAR1A inactivating mutations. PRKC fusions activate the Gαq/11 pathway similar to blue nevi. Conversely, inactivating mutations in PRKAR1A activate the Gαs pathway. We hypothesize that PRKC fusions have greater genomic overlap with
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The Genetic Landscape of Primary Breast Marginal Zone Lymphoma Identifies a Mutational-driven Disease With Similarities to Ocular Adnexal Lymphoma. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-06-12 Vanesa-Sindi Ivanova, Thomas Menter, Joel Zaino, Kirsten D Mertz, Baptiste Hamelin, Stefan Dirnhofer, Veronika Kloboves-Prevodnik, Alexandar Tzankov, Gorana Gašljević
Extranodal marginal zone lymphomas (eMZL) can occur in any organ and site of the body. Recent research has shown that they differ from organ to organ in terms of their mutational profile. In this study, we investigated a cohort of primary breast marginal zone lymphomas (PBMZL) to get a better insight into their morphologic and molecular profile. A cohort of 15 cases (14 female and 1 male) was characterized
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PRKACA/PRKACB Fusions in Pancreatobiliary Intraductal Oncocytic Papillary Neoplasms Including Those With Atypical Morphology: An Analysis of 22 Cases Expanding Morphologic Spectrum. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-06-06 Mariko Tanaka, Kimiko Takeshita, Akiko Kunita, Kiyoshi Hasegawa, Tetsuo Ushiku
Intraductal oncocytic papillary neoplasms (IOPNs) of the pancreatobiliary tract are considered a separate entity from intraductal papillary mucinous neoplasms (IPMNs), especially because of the distinct molecular alterations represented by PRKACA or PRKACB fusion. However, IOPNs display a spectrum of cytoarchitectural features. Typically, an IOPN is composed of arborizing papillae lined by layers of
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Multifocal Papillary Thyroid Carcinomas With Discordant Molecular Drivers: Emphasizing the Morphology and Collision Tumors. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-05-31 Jonathan P Rivera, Yi-Chen Yeh, Paul Chih-Hsueh Chen, Jen-Fan Hang
Multifocal papillary thyroid carcinomas (PTCs) are common and the majority of the tumors harbor mutual BRAF p.V600E mutation. This study aimed to investigate a contemporary series of multifocal PTCs with discordant molecular drivers. Consecutive thyroidectomies diagnosed with multifocal PTCs ≥0.5 cm between 2019 and 2023 were reviewed. Immunohistochemistry (IHC) for BRAF VE1 was performed for all tumors
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Large and Extensive Multilocular Peritoneal Inclusion Cysts Lack Genomic Alterations and Follow an Indolent Clinical Course Despite Rare Recurrences. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-05-30 Kyle M Devins, Esther Baranov, Yin P Hung, Brendan C Dickson, Esther Oliva, Vikram Deshpande
Peritoneal inclusion cysts (PICs) are unilocular or multilocular cystic lesions lined by bland mesothelial cells. While most are small and localized, rare examples may be large or multifocal with diffuse peritoneal involvement, causing clinical and even pathologic concern for malignancy. We examined 20 PIC, including 8 large solitary and 12 multifocal lesions. Solitary PIC were found in 7 female and
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Clinicopathological and Molecular Features of Penile Melanoma With a Proposed Staging System. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-05-29 Kristine M Cornejo, Amrita Goyal, Aida Valencia Guerrero, Michael Astudillo, Dora Dias-Santagata, Matthew M Johnson, Adam S Feldman, Mai P Hoang
Penile melanomas (PM) are an exceedingly rare subtype of mucosal melanoma (MM), and we reviewed the clinicopathologic features and molecular profile in 8 PMs. The patient ages ranged from 46 to 78 (mean: 62.8) years with involvement on the glans (n=5; 62.5%), penile urethra (n=2; 25%), and foreskin (n=1, 12.5%). Tumor depth ranged from 1.6 to 10.0 (mean: 5.25) mm. Most of the patients underwent partial
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Artificial Intelligence Helps Pathologists Increase Diagnostic Accuracy and Efficiency in the Detection of Breast Cancer Lymph Node Metastases. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-05-29 Juan Antonio Retamero, Emre Gulturk, Alican Bozkurt, Sandy Liu, Maria Gorgan, Luis Moral, Margaret Horton, Andrea Parke, Kasper Malfroid, Jill Sue, Brandon Rothrock, Gerard Oakley, George DeMuth, Ewan Millar, Thomas J Fuchs, David S Klimstra
The detection of lymph node metastases is essential for breast cancer staging, although it is a tedious and time-consuming task where the sensitivity of pathologists is suboptimal. Artificial intelligence (AI) can help pathologists detect lymph node metastases, which could help alleviate workload issues. We studied how pathologists' performance varied when aided by AI. An AI algorithm was trained using
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Increased Active Inflammation in the Colon is Not a Reliable Predictor of an Elevated Risk of Dysplasia in Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-05-29 Ruth Zhang, Dongliang Wang, Gregory Y Lauwers, Won-Tak Choi
Although the increased risk of colorectal neoplasia in patients with both primary sclerosing cholangitis (PSC) and ulcerative colitis (UC; termed PSC-UC) is well documented, the mechanism through which concomitant PSC increases the risk of colorectal neoplasia remains unclear. Given that the risk of colorectal neoplasia in UC is positively correlated with increased histologic inflammation, this study
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Crystalline Hepatopathy Associated With Bietti Crystalline Dystrophy: A Striking Manifestation of Disordered Fatty Acid Metabolism. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-05-28 Ben W Dulken, Dorukhan Bahceci, Loh-Shan Leung, Vinit B Mahajan, Won-Tak Choi, Serena Y Tan
Bietti crystalline dystrophy (BCD) is a rare heritable retinal disease characterized by crystal deposition primarily in the retina. It is associated with atrophy of the retinal pigment epithelium (RPE) and is caused by variants in CYP4V2, which encodes a cytochrome P450 hemethiolate protein superfamily member. CYP4V2 is involved in the selective hydrolysis of saturated medium chain fatty acids, and
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Molecular Classification Outperforms Histologic Classification in Prognostication of High-grade Endometrial Carcinomas With Undifferentiated and Sarcomatous Components. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-05-23 Phoebe M Hammer, Aihui Wang, Lisa Vermij, Sabrina Zdravkovic, Lucas Heilbroner, Emily Ryan, Rachel L P Geisick, Vivek Charu, Teri A Longacre, Carlos J Suarez, Chandler Ho, Taylor M Jenkins, Anne M Mills, Tjalling Bosse, Brooke E Howitt
Since the establishment of 4 molecular subgroups of endometrial carcinoma (EC), there has been significant interest in understanding molecular classification in the context of histologic features and diagnoses. ECs with undifferentiated, spindle, and/or sarcomatous components represent a diagnostically challenging subset of tumors with overlapping clinical and histologic features. We examined the clinicopathologic
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Primary Squamous Cell Carcinoma of the Thyroid Has a Molecular Genetic Profile Distinct From That of Anaplastic Thyroid Carcinoma: A Whole Exome Sequencing and Gene Expression Profiling Study. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-05-22 Meihua Ye, Zhenying Guo, Jingjing Xu, Yanling Jin, Xianglei He, Minghua Ge
Primary squamous cell carcinoma (SCC) of the thyroid and anaplastic thyroid carcinoma (ATC) show significant clinical and histologic overlap. Their biological behaviors are so similar that the fifth WHO updates SCC as a morphologic pattern of ATC rather than a separate entity. However, molecular genomic evidence that determines them as the same histologic type is limited. We aimed to explore whether
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Pseudosquamous Adenocarcinoma of the Lung: Clinicopathologic and Immunohistochemical Study of 10 Cases. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-05-20 David I Suster, Natali Ronen, Saul Suster
Pseudosquamous adenocarcinoma of the lung is an unusual morphologic variant of poorly differentiated non-small cell lung carcinoma that superficially resembles a squamous cell carcinoma. We have examined 10 cases of these tumors in 4 women and 6 men, aged 47 to 93 years. The tumors were all peripheral and measured from 1.5 to 5.5 cm. All cases were characterized by solid nests of large polygonal tumor
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PanIN or IPMN? Redefining Lesion Size in 3 Dimensions. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-05-20 Ashley L Kiemen, Lucie Dequiedt, Yu Shen, Yutong Zhu, Valentina Matos-Romero, André Forjaz, Kurtis Campbell, Will Dhana, Toby Cornish, Alicia M Braxton, Pei-Hsun Wu, Elliot K Fishman, Laura D Wood, Denis Wirtz, Ralph H Hruban
Pancreatic ductal adenocarcinoma (PDAC) develops from 2 known precursor lesions: a majority (∼85%) develops from pancreatic intraepithelial neoplasia (PanIN), and a minority develops from intraductal papillary mucinous neoplasms (IPMNs). Clinical classification of PanIN and IPMN relies on a combination of low-resolution, 3-dimensional (D) imaging (computed tomography, CT), and high-resolution, 2D imaging
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Extraskeletal Ewing Sarcoma of the Gastrointestinal and Hepatobiliary Tract: Deceptive Immunophenotype Commonly Leads to Misdiagnosis. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-05-17 Oyewale Shiyanbola, Recep Nigdelioglu, Deepti Dhall, Iván A González, Laura M Warmke, Shula Schechter, Won-Tak Choi, Shaomin Hu, Lysandra Voltaggio, Yujie Zhang, Tom Z Liang, Huaibin M Ko, Greg W Charville, Teri A Longacre
Ewing sarcoma (ES) is an uncommon mesenchymal neoplasm that typically develops as a bone mass, although up to 30% arise in extraskeletal sites. ES of the gastrointestinal (GI) and hepatobiliary tract is rare and may be misdiagnosed as other, more common neoplasms that occur in these sites. However, the correct classification of extraskeletal ES is important for timely clinical management and prognostication
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A Novel Objective Pathologic Criterion for Isolated Hypoganglionosis. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-05-10 Akihiko Tamaki, Kenichi Kohashi, Koichiro Yoshimaru, Yuko Hino, Hiroshi Hamada, Naonori Kawakubo, Tomoaki Taguchi, Tatsuro Tajiri, Yoshinao Oda
Isolated hypoganglionosis (IHG) is histologically characterized by small numbers of myenteric ganglion cells and small myenteric ganglia; however, no numerical diagnostic criteria for IHG have been established. Therefore, this study aimed to develop quantitative pathologic criteria for IHG. We evaluated 160 resected intestinal tissue specimens from 29 pediatric autopsies and 10 IHG cases. These specimens
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Histologic Features of Mycobacterial Spindle Cell Pseudotumors: A Multi-institutional Clinicopathologic Analysis of 14 Cases. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-05-10 Julianne M Szczepanski, Joshua A Lieberman, Laura W Lamps, Raul S Gonzalez, Yue Xue, Xuchen Zhang, Osman H Yilmaz, John Hart, Thomas Krausz, Jose G Mantilla, Jonathan B McHugh, Maria Westerhoff
Mycobacterial spindle cell pseudotumors (MSPs) are a rare and diagnostically challenging manifestation of non-tuberculous mycobacterial (NTM) infections. Proper recognition of these pseudotumors is important because they are treatable and benign. In this study, we evaluated the morphologic patterns of MSPs to improve their pathologic identification. Clinical and morphologic features of 14 MSPs were
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Transcriptionally Active Human Papillomavirus Infection in a Minority of Esophageal Squamous Cell Carcinomas in North America. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-05-10 Anna H Bauer, Khaled J Alkhateeb, Agoston T Agoston, Robert D Odze, Megha G Joshi, Brandon M Huffman, Peter Enzinger, Kimberly Perez, Vikram Deshpande, James M Cleary, Jon O Wee, Fei Dong, Lei Zhao
The role of Human papillomavirus (HPV) infection in esophageal squamous cell carcinoma (ESCC) is a topic of ongoing debate. This study used two screening approaches to look for evidence of HPV infection in esophageal squamous cell carcinoma. We initially checked for HPV infection in a randomly selected group of 53 ESCC cases. We did not detect any tumors positive for high-risk HPV. However, during
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Benign Islet Cells Within Peripancreatic Lymph Nodes: A Potential Diagnostic Pitfall. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-05-09 Ezra Baraban, Elizabeth D Thompson, Andres Matoso, Ralph H Hruban, Pedram Argani
The presence of epithelial cells within lymph node parenchyma is typically indicative of a metastatic malignancy. However, there are rare instances in which non-neoplastic epithelial or epithelioid cells may be found within lymph nodes, either due to aberrant embryologic migration, mechanical displacement, or physiological trafficking. These can potentially lead to serious potential diagnostic pitfalls
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Myxoid Inflammatory Myofibroblastic Sarcoma: Clinicopathologic Analysis of 25 Cases of a Distinctive Sarcoma With Deceptively Bland Morphology and Aggressive Clinical Behavior. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-05-08 David J Papke, Igor Odintsov, Brendan C Dickson, Marisa R Nucci, Abbas Agaimy, Christopher D M Fletcher
The number of recognized sarcoma types harboring targetable molecular alterations continues to increase. Here we present 25 examples of a distinctive myofibroblastic tumor, provisionally termed "myxoid inflammatory myofibroblastic sarcoma," which might be related to inflammatory myofibroblastic tumor, and which occurred in 13 males (52%) and 12 females at a median age of 37 years (range: 7 to 79 years)
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PON3::LCN1 and HTN3::MSANTD3 Gene Fusions With NR4A3/NR4A2 Expression in Salivary Acinic Cell Carcinoma. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-04-29 Lijing Zhu, Lisha Sun, Ye Zhang, Xiaoxiao Liu, XueFen Li, Zheng Zhou, Yajuan Cui, Chuan-Xiang Zhou, Tie-Jun Li
Acinic cell carcinoma of the salivary gland (AciCC) is a low-grade carcinoma characterized by the overexpression of the transcription factor nuclear receptor subfamily 4 group A member 3 (NR4A3). AciCC has been the subject of a few molecular research projects. This study delves into AciCC's molecular landscape to identify additional alterations and explore their clinical implications. RNA sequencing
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Yolk Sac Differentiation in Endometrial Carcinoma: Incidence and Clinicopathologic Features of Somatically Derived Yolk Sac Tumors Versus Carcinomas With Nonspecific Immunoexpression of Yolk Sac Markers. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-04-23 Anne M Mills, Taylor M Jenkins, Megan E Dibbern, Kristen A Atkins, Kari L Ring
Endometrial somatically derived yolk sac tumors are characterized by yolk sac morphology with AFP, SALL-4, and/or Glypican-3 immunoexpression. Yolk sac marker expression, however, is not limited to tumors with overt yolk sac histology. Three hundred consecutive endometrial malignancies were assessed for immunomarkers of yolk sac differentiation. Of these, 9% expressed ≥1 yolk sac marker, including
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TRPS1 is a Highly Sensitive Marker for Breast Cancer: A Tissue Microarray Study Evaluating More Than 19,000 Tumors From 152 Different Tumor Entities. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-04-22 Maximilian Lennartz, Neele Löhr, Doris Höflmayer, Sebastian Dwertmann Rico, Clara von Bargen, Simon Kind, Viktor Reiswich, Florian Viehweger, Florian Lutz, Veit Bertram, Christoph Fraune, Natalia Gorbokon, Sören Weidemann, Niclas C Blessin, Claudia Hube-Magg, Anne Menz, Ria Schlichter, Till Krech, Andrea Hinsch, Eike Burandt, Guido Sauter, Ronald Simon, Martina Kluth, Andreas H Marx, Patrick Lebok
Trichorhinophalangeal syndrome 1 (TRPS1) is a nuclear protein highly expressed in breast epithelial cells. TRPS1 immunohistochemistry (IHC) has been suggested as a breast cancer marker. To determine the diagnostic and prognostic utility of TRPS1 IHC, tissue microarrays containing 19,201 samples from 152 different tumor types and subtypes were analyzed. GATA3 IHC was performed in a previous study. TRPS1
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Genomic Catastrophe (Chromothripsis and Polyploidy) Correlates With Tumor Distribution in Extrauterine High-grade Serous Carcinoma. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-04-18 Ju-Yoon Yoon, Aarti Sharma, Azra H Ligon, Rebecca G Ramesh, T Rinda Soong, Wa Xian, David B Chapel, Christopher P Crum
Most extrauterine high-grade serous carcinomas (HGSCs) are thought to develop first in the distal fallopian tube. Most models of HGSC assume origin from relatively stable, noninvasive serous tubal intraepithelial carcinomas. However, widespread tumor involvement in the absence of a serous tubal intraepithelial carcinoma could occur after catastrophic genomic events (CGEs; such as chromothripsis or
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Patients with Classic Hodgkin Lymphoma and Follicular Lymphoma Compared to Single Malignancy Controls. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-04-11 Claudiu V Cotta, Shweta Bhavsar, Scott Robertson, James R Cook
Classic Hodgkin lymphoma (CHL) can arise in patients with low-grade B-cell lymphoma. The features of CHL arising in follicular lymphoma (FL) and its outcome are still unclear, mainly due to the very few cases reported. This study compares 17 patients with CHL and FL to 2 control groups: 1 of 26 patients with FL and a second of 60 patients older than 40 when diagnosed with CHL. Of the FL and CHL patients
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TFE3-Rearranged PEComa/PEComa-like Neoplasms: Report of 25 New Cases Expanding the Clinicopathologic Spectrum and Highlighting its Association With Prior Exposure to Chemotherapy. Am. J. Surg. Pathol. (IF 4.5) Pub Date : 2024-04-10 Pedram Argani, John M Gross, Ezra Baraban, Lisa M Rooper, Suping Chen, Ming-Tseh Lin, Christopher Gocke, Abbas Agaimy, Tamara Lotan, Albert J H Suurmeijer, Cristina R Antonescu
Since their original description as a distinctive neoplastic entity, ~50 TFE3-rearranged perivascular epithelioid cell tumors (PEComas) have been reported. We herein report 25 new TFE3-rearranged PEComas and review the published literature to further investigate their clinicopathologic spectrum. Notably, 5 of the 25 cases were associated with a prior history of chemotherapy treatment for cancer. This